Bilirubin exists as albumin-bound complexes in the bloodstream of patients with hyperbilirubinemia. Developing adsorbents with high removal efficiency for albumin-bound bilirubin and excellent hemocompatibility is essential for effective hemoperfusion therapy. Herein, microfibrillated cellulose-reinforced polyethyleneimine cryogels (PEI/MFC) with robust mechanical properties were fabricated through cryo-induced chemical crosslinking, using bis(vinylsulphonyl)methane (BVSM) as chemical cross-linker. The cryogel showed excellent fatigue resistance, retaining its shape after 100 underwater compression-decompression cycles at 80 % strain. The inherent properties of raw materials confer the PEI/MFC cryogel with exceptional blood compatibility in hemolysis, coagulation, and blood cell adhesion. Compared with conventional materials modified with PEI, our innovative PEI/MFC cryogel presents a higher density of amino groups, resulting in superior removal efficacy for bilirubin. The PEI/MFC cryogel achieved a remarkable removal efficiency of 99.6 % for free bilirubin and 64.3 % for albumin-bound bilirubin, at bilirubin concentrations of 200 mg/L and cryogel dosages of 2 mg/mL. The maximum adsorption capacity for albumin-bound bilirubin was determined to be 210.5 mg/g, representing a notable achievement. Furthermore, fixed-bed column adsorptions exhibit a 50 % breakthrough volume of 760.9 mL/g for free bilirubin and 334.6 mL/g for albumin-bound bilirubin. The successful simulation of hemoperfusion using the PEI/MFC cryogel indicates its potential for the treatment of hyperbilirubinemia.